S07-05 Neural stem cell polarity and malignant growth in Drosophila

Recent studies have uncovered a key role of endocytosis during Notch signalling after the asymmetric division of the fly sensory organ precursor cells (SOP): directional signalling is mediated by differential endocytosis of the ligand Delta and the Notch effector Sanpodo in one of the SOP daughters, the pIIb. Here we show a novel mechanism of directional signalling based on the trafficking of Delta/Notch molecules already internalized in the SOP and targeted subsequently to the pIIa daughter. We show that, in the SOP, internalized Delta and Notch traffic to an endosome characterized by the localization of the endosomal protein Sara. During SOP division, Sara endosomes and Notch/Delta therein move first to the central spindle and then to the pIIa cell in a process mediated by the Par-complex. Subsequently, in pIIa (but not pIIb), Notch appears cleaved in Sara endosomes in a process that requires gamma-secretase and Delta internalization implying that the intracellular Notch tail has been released to mediate transcription of Notch target genes. We thus uncovered two phases during biased Notch signalling: (i) in the mother, receptor molecules internalized into Sara endosomes are targeted to the pIIa, thereby increasing the level of Notch signaling in pIIa and decreasing it in pIIb and, (ii) subsequently, biased signaling is also mediated by endocytic trafficking leading to Sanpodo downregulation and Delta recycling/activation in the pIIb daughter cell.